TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2315	7168;7169;7170	chr2:178774321;178774320;178774319	chr2:179639048;179639047;179639046
N2AB	2315	7168;7169;7170	chr2:178774321;178774320;178774319	chr2:179639048;179639047;179639046
N2A	2315	7168;7169;7170	chr2:178774321;178774320;178774319	chr2:179639048;179639047;179639046
N2B	2269	7030;7031;7032	chr2:178774321;178774320;178774319	chr2:179639048;179639047;179639046
Novex-1	2269	7030;7031;7032	chr2:178774321;178774320;178774319	chr2:179639048;179639047;179639046
Novex-2	2269	7030;7031;7032	chr2:178774321;178774320;178774319	chr2:179639048;179639047;179639046
Novex-3	2315	7168;7169;7170	chr2:178774321;178774320;178774319	chr2:179639048;179639047;179639046

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-12
• Domain position: 49
• Structural Position: 125
• Q(SASA): 0.517
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/A	None	None	None	N	0.095	0.142	0.219573609325	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/K	None	None	0.351	N	0.398	0.312	0.465549362696	gnomAD-4.0.0	1.59058E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85673E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.0859	likely_benign	0.0877	benign	-0.746	Destabilizing	None	N	0.095	neutral	N	0.506275956	None	None	N
T/C	0.4618	ambiguous	0.4836	ambiguous	-0.355	Destabilizing	0.836	D	0.407	neutral	None	None	None	None	N
T/D	0.4227	ambiguous	0.422	ambiguous	-0.193	Destabilizing	0.418	N	0.394	neutral	None	None	None	None	N
T/E	0.3691	ambiguous	0.3686	ambiguous	-0.23	Destabilizing	0.418	N	0.39	neutral	None	None	None	None	N
T/F	0.178	likely_benign	0.1811	benign	-1.016	Destabilizing	0.716	D	0.467	neutral	None	None	None	None	N
T/G	0.2562	likely_benign	0.263	benign	-0.956	Destabilizing	0.129	N	0.363	neutral	None	None	None	None	N
T/H	0.2556	likely_benign	0.2568	benign	-1.31	Destabilizing	0.94	D	0.423	neutral	None	None	None	None	N
T/I	0.1139	likely_benign	0.1173	benign	-0.291	Destabilizing	0.085	N	0.396	neutral	N	0.507519865	None	None	N
T/K	0.2891	likely_benign	0.2854	benign	-0.649	Destabilizing	0.351	N	0.398	neutral	N	0.503918272	None	None	N
T/L	0.0996	likely_benign	0.1025	benign	-0.291	Destabilizing	0.129	N	0.369	neutral	None	None	None	None	N
T/M	0.096	likely_benign	0.0995	benign	0.119	Stabilizing	0.716	D	0.423	neutral	None	None	None	None	N
T/N	0.1147	likely_benign	0.1186	benign	-0.483	Destabilizing	0.418	N	0.216	neutral	None	None	None	None	N
T/P	0.5332	ambiguous	0.5551	ambiguous	-0.412	Destabilizing	0.523	D	0.423	neutral	D	0.590049585	None	None	N
T/Q	0.2657	likely_benign	0.2646	benign	-0.724	Destabilizing	0.836	D	0.46	neutral	None	None	None	None	N
T/R	0.2423	likely_benign	0.2375	benign	-0.366	Destabilizing	0.523	D	0.428	neutral	N	0.48735299	None	None	N
T/S	0.0924	likely_benign	0.0944	benign	-0.734	Destabilizing	0.003	N	0.129	neutral	N	0.473545884	None	None	N
T/V	0.1	likely_benign	0.1017	benign	-0.412	Destabilizing	0.001	N	0.068	neutral	None	None	None	None	N
T/W	0.6131	likely_pathogenic	0.608	pathogenic	-0.945	Destabilizing	0.983	D	0.43	neutral	None	None	None	None	N
T/Y	0.2679	likely_benign	0.2646	benign	-0.71	Destabilizing	0.836	D	0.448	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.